Evaluation of the potential use of a meta-population for genomic selection in autochthonous beef cattle populations.

This study investigated the potential application of genomic selection under a multi-breed scheme in the Spanish autochthonous beef cattle populations using a simulation study that replicates the structure of linkage disequilibrium obtained from a sample of 25 triplets of sire/dam/offspring per population and using the BovineHD Beadchip. Purebred and combined reference sets were used for the genomic evaluation and several scenarios of different genetic architecture of the trait were investigated. The single-breed evaluations yielded the highest within-breed accuracies. Across breed accuracies were found low but positive on average confirming the genetic connectedness between the populations. If the same genotyping effort is split in several populations, the accuracies were lower when compared with single-breed evaluation, but showed a small advantage over small-sized purebred reference sets over the accuracies of subsequent generations. Besides, the genetic architecture of the trait did not show any relevant effect on the accuracy with the exception of rare variants, which yielded slightly lower results and higher loss of predictive ability over the generations.

Genomic differentiation between Asturiana de los Valles, Avileña-Negra Ibérica, Bruna dels Pirineus, Morucha, Pirenaica, Retinta and Rubia Gallega cattle breeds.

The Spanish local beef cattle breeds have most likely common origin followed by a process of differentiation. This particular historical evolution has most probably left detectable signatures in the genome. The objective of this study was to identify genomic regions associated with differentiation processes in seven Spanish autochthonous populations (Asturiana de los Valles (AV), Avileña-Negra Ibérica (ANI), Bruna dels Pirineus (BP), Morucha (Mo), Pirenaica (Pi), Retinta (Re) and Rubia Gallega (RG)). The BovineHD 777K BeadChip was used on 342 individuals (AV, n=50; ANI, n=48; BP, n=50; Mo, n=50; Pi, n=48; Re, n=48; RG, n=48) chosen to be as unrelated as possible. We calculated the fixation index (F ST ) and performed a Bayesian analysis named SelEstim. The output of both procedures was very similar, although the Bayesian analysis provided a richer inference and allowed us to calculate significance thresholds by generating a pseudo-observed data set from the estimated posterior distributions. We identified a very large number of genomic regions, but when a very restrictive significance threshold was applied these regions were reduced to only 10. Among them, four regions can be highlighted because they comprised a large number of single nucleotide polymorphisms and showed extremely high signals (Kullback-Leiber divergence (KLD)>6). They are located in BTA 2 (5 575 950 to 10 152 228 base pairs (bp)), BTA 5 (17 596 734 to 18 850 702 bp), BTA 6 (37 853 912 to 39 441 548 bp) and BTA 18 (13 345 515 to 15 243 838 bp) and harbor, among others, the MSTN (Myostatin), KIT-LG (KIT Ligand), LAP3 (leucine aminopeptidase 3), NAPCG (non-SMC condensing I complex, subunit G), LCORL (ligand dependent nuclear receptor corepressor-like) and MC1R (Melanocortin 1 receptor) genes. Knowledge on these genomic regions allows to identify potential targets of recent selection and helps to define potential candidate genes associated with traits of interest, such as coat color, muscle development, fertility, growth, carcass and immunological response.

Bayesian analysis of parent-specific transmission ratio distortion in seven Spanish beef cattle breeds.

Transmission ratio distortion (TRD) is the departure from the expected Mendelian ratio in offspring, a poorly investigated biological phenomenon in livestock species. Given the current availability of specific parametric methods for the analysis of segregation data, this study focused on the screening of TRD in 602 402 single nucleotide polymorphisms covering all autosomal chromosomes in seven Spanish beef cattle breeds. On average, 0.13% (n = 786) and 0.01% (n = 29) of genetic markers evidenced sire- or dam-specific TRD respectively. There were no single nucleotide polymorphisms accounting for both sire- and dam-specific TRD at the same time, and only one marker (rs43147474) accounted for (sire-specific) TRD in all seven breeds. It must be noted that rs43147474 is located in the fourth intronic region of the GTP-binding protein 10 gene, and this locus has been previously linked to the maintenance of mitochondria and nucleolar architectures. Alternatively, other candidate genes surround this hot-spot for sire-specific TRD in the cattle genome, and they are related to embryonic and postnatal lethality as well as prostate cancer, among others. This research characterized the distribution of TRD in the bovine genome, highlighting heterogeneous results when comparing across breeds.

Linkage disequilibrium, persistence of phase, and effective population size in Spanish local beef cattle breeds assessed through a high-density single nucleotide polymorphism chip.

Linkage disequilibrium (LD) and persistence of phase are fundamental approaches for exploring the genetic basis of economically important traits in cattle, including the identification of QTL for genomic selection and the estimation of effective population size () to determine the size of the training populations. In this study, we have used the Illumina BovineHD chip in 168 trios of 7 Spanish beef cattle breeds to obtain an overview of the magnitude of LD and the persistence of LD phase through the physical distance between markers. Also, we estimated the time of divergence based on the persistence of the LD phase and calculated past from LD estimates using different alternatives to define the recombination rate. Estimates of average (as a measure of LD) for adjacent markers were close to 0.52 in the 7 breeds and decreased with the distance between markers, although in long distances, some LD still remained (0.07 and 0.05 for markers 200 kb and 1 Mb apart, respectively). A panel with a lower boundary of 38,000 SNP would be necessary to launch a successful within-breed genomic selection program. Persistence of phase, measured as the pairwise correlations between estimates of in 2 breeds at short distances (10 kb), was in the 0.89 to 0.94 range and decreased from 0.33 to 0.52 to a range of 0.01 to 0.08 when marker distance increased from 200 kb to 1 Mb, respectively. The magnitude of the persistence of phase between the Spanish beef breeds was similar to those found in dairy breeds. For across-breed genomic selection, the size of the SNP panels must be in the range of 50,000 to 83,000 SNP. Estimates of past showed values ranging from 26 to 31 for 1 generation ago in all breeds. The divergence among breeds occurred between 129 and 207 generations ago. The results of this study are relevant for the future implementation of within- and across-breed genomic selection programs in the Spanish beef cattle populations. Our results suggest that a reduced subset of the SNP panel would be enough to achieve an adequate precision of the genomic predictions.

Genetic diversity and divergence among Spanish beef cattle breeds assessed by a bovine high-density SNP chip.

The availability of SNP chips for massive genotyping has proven to be useful to genetically characterize populations of domestic cattle and to assess their degree of divergence. In this study, the Illumina BovineHD BeadChip genotyping array was used to describe the genetic variability and divergence among 7 important autochthonous Spanish beef cattle breeds. The within-breed genetic diversity, measured as the marker expected heterozygosity, was around 0.30, similar to other European cattle breeds. The analysis of molecular variance revealed that 94.22% of the total variance was explained by differences within individuals whereas only 4.46% was the result of differences among populations. The degree of genetic differentiation was small to moderate as the pairwise fixation index of genetic differentiation among breeds (F) estimates ranged from 0.026 to 0.068 and the Nei's D genetic distances ranged from 0.009 to 0.016. A neighbor joining (N-J) phylogenetic tree showed 2 main groups of breeds: Pirenaica, Bruna dels Pirineus, and Rubia Gallega on the one hand and Avileña-Negra Ibérica, Morucha, and Retinta on the other. In turn, Asturiana de los Valles occupied an independent and intermediate position. A principal component analysis (PCA) applied to a distance matrix based on marker identity by state, in which the first 2 axes explained up to 17.3% of the variance, showed a grouping of animals that was similar to the one observed in the N-J tree. Finally, a cluster analysis for ancestries allowed assigning all the individuals to the breed they belong to, although it revealed some degree of admixture among breeds. Our results indicate large within-breed diversity and a low degree of divergence among the autochthonous Spanish beef cattle breeds studied. Both N-J and PCA groupings fit quite well to the ancestral trunks from which the Spanish beef cattle breeds were supposed to derive.

Porcine circovirus type 2 (PCV2) enteric disease: an independent condition or part of the systemic disease?

Intestinal disorders in growing and finishing pigs have been associated with several infectious agents, including Porcine circovirus type 2 (PCV2). This virus has been mainly related with PCV2-systemic disease (PCV2-SD); nevertheless, some authors have suggested a possible restricted intestinal infection of this virus associated with enteric clinical signs. This condition has been referred as PCV2-enteric disease (PCV2-ED). The present study analysed retrospectively, from a pathological point of view, the relation between intestinal disorders and PCV2 infection in nursery and growing-finishing pigs. Among the 96 selected pigs suffering from enteric disease and submitted for necropsy between 1998 and 2011, the most prevalent enteric lesions were catarrhal enteritis/colitis (77.1%), followed by fibrinous lesions (11.5%), granulomatous inflammation (4.2%) and other lesions such as haemorrhages or ulceration (4.2%). Seventy-two pigs (75%) were positive for PCV2 by in situ hybridization (ISH). Among positive pigs for PCV2 ISH, 39 animals suffered from PCV2-SD and 33 had no lymphoid lesions but low amount of viral nucleic acid in several lymphoid tissues, therefore, these animals did not qualify for PCVD-ED. In conclusion, all animals with enteric disorders that were positive to PCV2 by ISH had evidence of viral systemic infection. These results suggest that PCV2-ED is probably a negligible condition and PCV2 mainly contributes to enteric clinical disorders in relation to PCV2-SD occurrence.

Monitoring changes in the demographic and genealogical structure of the main Spanish local beef breeds.

Demographic and pedigree analyses describe the structure and dynamics of livestock populations. We studied information recorded in the herdbooks of Asturiana de los Valles (AV; N = 458,806), Avileña-Negra Ibérica (ANI; N = 204,623), Bruna dels Pirineus (BP; N = 62,138), Morucha (Mo; N = 65,350), Pirenaica (Pi; N = 217,428), Retinta (Re; N = 135,300), and Rubia Gallega (RG; N = 235,511) beef breeds from their creation until 2009. All breeds have increased in the number of registered cows in recent years. In all breeds, herds do not behave as isolated entities and a high rate of exchange of breeding males between herds exists. A percentage of herds (12-52%) make some type of selection and sell bulls to other herds. There were large differences in average number of progeny per bull, ranging from 15.6 (AV) to 373.7 animals (RG, with a high incidence of AI). Generation interval estimates ranged from 4.7 (AV) to 7.6 (RG) yr in the sire pathway and from 5.95 (AV) to 7.8 (Mo) yr in the dam pathway. Density of pedigrees varied among breeds, with Pi, ANI, and Re having the more dense pedigrees, with average completeness indexes of more than 96% in the first generation and 80% when 6 generations were considered. A general increase in average inbreeding was observed in all breeds in the years analyzed. For animals born in 2009, average inbreeding coefficients ranged from 0.6 (BP) to 7.2% (Re) when all animals were considered and from 3.6 (Pi) to 17.6% (BP) when only inbred animals were considered. Due to the lack of completeness of pedigrees in most populations, inbreeding coefficients may be considered as a lower bound of the true parameters. The proportion of inbred animals tended to increase in the periods analyzed in all breeds. Differences between inbreeding and coancestry rates (except in RG) suggest the presence of population structure. Effective population size (Ne) based on the inbreeding rate estimated by regression ranged from 43 to 378 for Re and BP, whereas Ne estimates based on coancestry were greater, with a range of 100 for RG to 9,985 for BP. These facts suggest that an adequate mating policy can help to monitor inbreeding so as not to lose genetic variability. Effective number of ancestors in 2009 for 6 of the breeds ranged from 42 (RG) to 220 (AV), with BP having much a greater value, and was lower than was the effective number of founders in all breeds, suggesting the existence of bottlenecks.

Multi-trait and random regression approaches for addressing the wide range of weaning ages in Asturiana de los Valles beef cattle for genetic parameter estimation.

Weaning weight (WW) records of 24,066 Asturiana de los Valles beef cattle, including the progeny of 557 sires and 10,653 dams, were analyzed using a multitrait animal model (MAM) and a random regression model (RRM) in order to estimate the variance components and the breeding value of the animals. Three definitions of WW were used: early weaning (EW) for animals weaned before the age of 180 d; standard weaning (SW) for animals weaned between 180 and 240 d old; and late weaning (LW) for animals weaned between the ages of 240 and 365 d. The heritabilities (h(2)) were high (from 0.49 to 0.63), which fully agrees with previous estimates for this breed. The genetic correlations between EW and SW were 0.86, and lower between EW and LW at 0.543 to 0.622, using MAM and RRM models, respectively. Ranking of sires displayed changes depending on age at weaning of their offspring, which could explain the modest genetic progress reached using MAM evaluation. The first 2 eigenvalues of the random regression coefficient matrix explained 66 and 30% of the genetic variance, which implies important genetic variation underlying the form of the growth curve of the animals during the weaning period. The evaluation of sires according to the official method, as currently carried out by the breeders' association (WW adjusted previously to the age of 180 d), does not exploit the genetic differences in response to their production system where the calf is weaned at variable ages.

[Metastasis in maxilar sinus as only manifestation of disseminate renal adenocarcinoma]. / Metástasis en seno maxilar como única manifestación de adenocarcinoma renal diseminado.

Paranasal sinuses and nose metastasis are very uncommon. About 50 have been reported. Renal cell carcinoma is the primary neoplasm which most frequently metastasizes in the nasosinusal region, followed by breast and lug. Symptoms are unspecific, but the epistaxis constitutes the most common sign due to the significant vascularizations of the tumor. Prognosis is poor. The survival rate fluctuates between 15-30% at 5 years. Surgery is the elective treatment.

[Application of a critical incident reporting and analysis system in an anesthesiology department]. / Utilización de un sistema de comunicación y análisis de incidentes críticos en un servicio de anestesia.

OBJECTIVES: To ascertain the changes in anesthesia-related morbidity and mortality after application of a scheme for reporting critical incidents and to assess the effect of implementing preventive measures against the detected errors. PATIENTS AND METHODS: We defined a critical incident to be any situation in which the margin of safety for the patient was reduced or might have been reduced. We analyzed data from the period between January 1999 and December 2004. RESULTS: The number of critical incidents was 547 (0.79% of 68627 anesthetic procedures). Human error was identified in 279 incidents (51%). The most frequent factors underlying errors were wrong diagnosis of the situation, communication problems, and failure to check equipment and drugs. The patient suffered no adverse effect in 81.8% of the incidents; 78.9% were considered preventable. Introducing an equipment checklist before anesthesia reduced the number of incidents from 90 events in 21809 cases in 31 months to 34 events out of 22064 cases in 29 months; chi2 test, P < 0.05; odds ratio (OR), 2.68; 95% confidence interval (CI), 1.80-3.98). Labeling syringes reduced errors in the administration of medications from 45 errors in 21 809 cases in 31 months to 27 in 22064 cases in 29 months; chi2, P < 0.05; OR, 1.68; 95% CI, 1.04-2.72. CONCLUSIONS: Corrective measures were adopted as a result of the incident reporting scheme. Some of the measures led to a statistically significant reduction in equipment and drug administration errors.

[Esthesioneuroblastoma. Description of a case and review of the literature]. / Estesioneuroblastoma. Presentación de un caso clínico y revisión de la bibliografía.

The esthesioneuroblastoma is a malignant and rare type of the nasal cavity. Affected patients usually present with a progressive nasal obstruction, rhinorrea and epistaxis. Metastasis occurs in about 30% of patiens, the most common sites for metastasis are the cervical lymph nodes, less frequent in anothers organs. The optimum management is probably surgery combined with radiotherapy, the chemotherapy is usually reserved for local advanced tumor

Long-term outcome of allogeneic or autologous haemopoietic cell transplantation for acute lymphoblastic leukaemia in second remission in children. GETMON experience 1983-1998.

We present a retrospective study of long-term outcome and predictive factors of survival and relapse in 219 paediatric patients with acute lymphoblastic leukaemia (ALL) in second remission. They received allogeneic (allo) or autologous (auto) haemopoietic cell transplantation (HCT) depending on the availability of a matched sibling donor. The probability of event-free survival (EFS) for the total patient group was 0.35+0.03 at 14 years. No significant differences were observed for EFS between allo- and auto-HCT: 0.39+0.05 vs 0.32+0.04 (P=0.43). A better EFS was seen in patients with a late relapse (LR) (P=0.06 and 0.02, for allogeneic and autologous respectively). Significantly better EFS was observed in allo-HCT patients under 10 years of age and in auto-HCT patients with leukocytes at diagnosis below 25 x 109/l and late relapse. Predictive factors of failure in both groups were early relapse (ER), medullary relapse and age over 10 years. The probability of relapse (RP) for the total group of patients was 0.57+0.03, and it was significantly higher in auto-HCT patients: 0.65+0.04 vs 0.42+0.06 (P=0.002). Factors predictive for relapse were medullary and early relapse, auto-HCT and WBC >25 x 109/l at diagnosis.

Asymptotic variances of QTL estimators with selective DNA pooling.

Investigation on QTL-marker linkage usually requires a great number of observed recombinations, inferred from combined analysis of phenotypes and genotypes. To avoid costly individual genotyping, inferences on QTL position and effects can instead make use of marker allele frequencies. DNA pooling of selected samples makes allele frequency estimation feasible for studies involving large sample sizes. Linkage studies in outbred populations have traditionally exploited half-sib family designs; within the animal production context, half-sibships provide large families that are highly suitable for DNA pooling. Estimators for QTL position and effect have been proposed that make use of information from flanking markers. We present formulas derived by the delta method for the asymptotic variance of these estimators.

Simulating complex traits influenced by genes with fuzzy-valued effects in pedigreed populations.

MOTIVATION: Methods involving fuzzy theory have been rarely applied to genetics. We present an open platform for experimentation with fuzzy numbers as a tool to represent imprecise phenotypes in genetic modeling. RESULTS: A C++ library for simulation of genetic information transmission is introduced. The study of genetic linkage was its first goal, though a design so general as possible has been meant. Fuzzy-valued phenotypes are handled by means of fuzzy numbers. AVAILABILITY: ftp://carleos.etsiig.uniovi.es/pub/falin ftp://fisher.ciencias.uniovi.es/pub/falin ftp://bellman.ciencias.uniovi.es/pub/falin Licensed under the GNU General Public License version 2 (see http://www.gnu.org/licenses/gpl.html).

Disparity for the minor histocompatibility antigen HA-1 is associated with an increased risk of acute graft-versus-host disease (GvHD) but it does not affect chronic GvHD incidence, disease-free survival or overall survival after allogeneic human leucocyte antigen-identical sibling donor transplantation.

Disparity for the minor histocompatibility antigen HA-1 between patient and donor has been associated with an increased risk of acute graft-versus-host disease (GvHD) after allogeneic human leucocyte antigen (HLA)-identical sibling donor stem cell transplantation (SCT). However, no data concerning the impact of such disparity on chronic GvHD, relapse or overall survival are available. A retrospective multicentre study was performed on 215 HLA-A2-positive patients who received an HLA-identical sibling SCT, in order to determine the differences in acute and chronic GvHD incidence on the basis of the presence or absence of the HA-1 antigen mismatch. Disease-free survival and overall survival were also analysed. We detected 34 patient-donor pairs mismatched for HA-1 antigen (15.8%). Grades II-IV acute GvHD occurred in 51.6% of the HA-1-mismatched pairs compared with 37.1% of the non-mismatched. The multivariate logistic regression model showed statistical significance (P: 0.035, OR: 2.96, 95% CI: 1.07-8.14). No differences were observed between the two groups for grades III-IV acute GvHD, chronic GvHD, disease-free survival or overall survival. These results confirmed the association between HA-1 mismatch and risk of mild acute GvHD, but HA-1 mismatch was not associated with an increased incidence of chronic GvHD and did not affect relapse or overall survival.

Does allogrooming serve a hygienic function in Cercocebus torquatus lunulatus?

To test the hygienic functional hypothesis of allogrooming in the white-crowned mangabey (Cercocebus torquatus lunulatus), we analyzed the distribution of such behavior over the body surface in the individuals of two captive groups of this species (N = 9 and N = 8). To sample the data, we used focal animal sampling and continuous recording. Before analyzing the data, we measured a representative subject in order to calculate the body surface area occupied by each site, defined accessibility rigorously (distinguishing among three categories of sites: easy to reach, difficult to reach, and inaccessible), and tested empirically the classification proposed. To determine whether allogrooming was likely to concentrate on the body sites with accessibility problems, we ran three successive analyses, each of with was increasingly specific: grouping types of sites, analyzing each site separately, and analyzing each subject's reception profile. The results obtained show that in both groups inaccessible sites received more allogrooming than predicted by their actual surface area; sites that were difficult to reach received an amount of allogrooming proportional to the body surface area they occupied, and those easy to reach received less allogrooming than expected. This complementarity between the distribution of auto- and allogrooming is consistent with the hygienic functional hypothesis of allogrooming. However, not all inaccessible sides nor those difficult-to-reach were allogroomed equally: Allogrooming concentrated primarily on dorsal and caudal regions, whose care is incompatible with a ventral/ventral orientation between groomer and groomee. The strong distributional selectivity of allogrooming and the interindividual variability in preferred allogrooming sites suggest that the hygienic functional hypothesis cannot fully account for all the aspects of the corporal distribution of such behavior. Thus, in support of the multifunctional nature of allogrooming, we conclude that there must be more than cleaning involved in Cercocebus torquatus lunulatus' allogrooming.

Disappearance of lupus anticoagulant after allogeneic bone marrow transplantation.

Lupus anticoagulant antibodies have never been reported to disappear after either allogeneic or autologous bone marrow transplantation in humans. We report the first case of disappearance of lupus anticoagulant antibodies in a patient without systemic lupus erythematosus or clinical evidence of other autoimmune disorders, who received an allogeneic bone marrow transplant as treatment for chronic myeloid leukemia. Although marrow transplantation is not a recognized therapy for antiphospholipid syndrome, our observation should be considered another example of the capability of intensive chemo-radiotherapy followed by stem cell transplantation to ablate a pathologic marrow clone resulting in an autoimmune disorder and improve, or even cure, some severe autoimmune diseases.

Primary lymphoplasmacytoid lymphoma of the trachea with immunoglobulin G paraprotein.

A primary tracheal lymphoma with immunoglobulin G (IgG)-associated monoclonal serum paraprotein treated with surgery and chemotherapy is reported. As far as we know this is the first lymphoplasmacytoid lymphoma reported in the tracheobronchial tree and the first with a serum and tissue IgG monoclonal paraprotein. Differential diagnosis must be made essentially with extramedullary plasmacytoma and mucosa-associated lymphoid tissue lymphoma. CD-45RB strong positivity and the absence of lymphoepithelial lesions may help to differentiate lymphoplasmacytoid lymphoma from them. We expand the spectrum of lymphoid lesions with plasmacytoid features that can occur in the tracheobronchial tract.

Influence of high-carbohydrate enriched diets on plasma insulin levels and insulin and IGF-I receptors in trout.

Insulin and insulin growth factor-I (IGF-I) binding to skeletal muscle semipurified receptors were assessed in rainbow trout (Oncorhynchus mykiss) fed with different enriched carbohydrate diets. The animals were fed for 2 months, either in spring, summer or autumn with a control diet (C, commercial diet containing 21% raw carbohydrates) or with two diets supplied with highly digestible carbohydrates (E1, 22% expanded wheat; and E2, 37% expanded wheat). Insulin and IGF-I receptors were semipurified by affinity chromatography (WGA-agarose). Fish fed with a carbohydrate enriched diet did not show lower growth rates than those fed with the control diet. Independently of the season, rainbow trout fed E1 and E2 presented higher insulin and glucose plasma levels as well as higher tissue glycogen reserves than fish fed C. An increase in the number of insulin receptors during the diet adaptation was observed especially in fish fed with E2. No differences in the affinity of receptors were observed. IGF-I specific binding in skeletal muscle was higher than that of insulin in all groups and in all seasons. Furthermore, IGF-I receptors showed the same tendency as insulin receptors, with increases in their number in experimentally fed fish, especially those fed with E2. Insulin and IGF-I receptors TKA increased only slightly, as a consequence of E1 and E2 diet adaptation. In conclusion, rainbow trout can be fed high-carbohydrate levels and show good rates of growth. This adaptation determines increases in circulating glucose and insulin, and muscle insulin receptors, which indicate an adaptation of the fish to higher levels of glucose supply. The response of IGF-I receptors also suggests a possible role in the regulation of metabolism.